Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra‐Articular Space

Steroid injections are effective in diseases such as rheumatoid arthritis but limited by short duration of action and risks of joint degeneration with repeat application. It is demonstrated that steroids delivered in injectable non-Newtonian Gellan sheared hydrogels are highly suited to this application, being cell-compatible and possessing improved drug release profiles and anti-inflammatory efficacy in a murine model of polyarthritis.

Abstract

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application – capable of shear thinning under force but restructuring at rest to enhance residence. This study examined GSHs for extended intra-articular glucocorticoid delivery of prednisolone (10 mg mL⁻¹); demonstrating links between material mechanics, steroid release, and preclinical assessment of efficacy in synoviocyte culture and transgenic(TNF)197Gkl (TNFtg) murine model of arthritis. GSHs demonstrated sustained release, with typical Fickian profiles over 18 days. Moreover, systems showed good stability under extended culture, with inherent cell-compatibility and suppression of inflammatory synoviocyte activation. In TNFtg animals, GSHs suppressed synovitis (70.08%, p < 0.05), pannus formation (45.01%, p < 0.05), and increased articular cartilage (82.23%, p < 0.05) relative to vehicle controls. The extended profile of steroid release from injectable GSH formulations holds promise in the treatment and management of inflammatory arthritides such as rheumatoid and osteoarthritis, representing a step-change in intra-articular drug delivery to suppress long-term joint inflammation.